Heparin, a strongly acidic, linear sulfated polysaccharide anti-coagulant, is used in the prevention and treatment of thrombosis. Heparin was first isolated from the liver from which it derives its name (1). Heparin-like polysaccharides are shown to interact with numerous proteins and orchestrate many different biologic functions (2). A unique penta-saccharide domain present within heparin was found to bind to Antithrombin III (ATIII) in a highly specific manner to induce a conformational change that is sufficient to promote rapid inhibition of blood coagulation (3, 4). Sinay and coworkers pioneered the original chemical synthesis of the ATIII binding pentasaccharide and analogs (5, 6).
Heparin-induced thrombocytopenia (HIT) is an immunologic disorder associated with heparin treatment (7). HIT paradoxically increases thrombosis, which occurs in about 30% of the recognized HIT cases, and is a major cause of morbidity and mortality in patients treated with heparin. It has been shown that HIT is induced by antibodies directed against a PF4-heparin complex. The complex formation requires a 2-O sulfated iduronic acid residue (8). Engineering new heparin-like anticoagulants that are unable to form heparin-PF4 complexes, would be a major advance in anticoagulation therapy. There is also an increased concern for the potential spread of diseases of animal origin to humans, such as bovine encephalopathy, due to the use of animal derived heparin. The above-mentioned potential side effects of animal derived heparin prompted the chemical synthesis of heparin-based anticoagulants. Despite many advances made in chemical synthesis, this approach is cumbersome and time consuming.